“下一代软骨修复和关节成形术前患者。”

IF 0.4 4区 医学 Q4 SPORT SCIENCES
Devon E. Anderson MD, PhD , Adam Gridley MBA , Dennis C. Crawford MD, PhD
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引用次数: 2

摘要

NeoCart植入物(Histogenics Corporation, Waltham, MA;Ocugen Inc., Malvern, PA)是一种基于细胞的关节软骨缺损修复疗法。植入物由I型胶原支架组成,接种扩展的自体软骨细胞,并在静水压和低氧张力下进行预处理。该过程旨在创建一个自体软骨结构,用于有症状的软骨疾病患者的外科生物重建过程中。良好的临床前基础科学和动物研究表征了NeoCart的再生潜力,从而使其成为美国食品和药物管理局(FDA)批准的第一个用于关节软骨修复的自体组织治疗药物,从2003年的I期安全性试验开始。相对于“标准治疗”微骨折,一项III期随机对照优势试验被认为是安全的,II期有效,FDA于2010年批准了一项针对微骨折的III期随机对照优势试验。根据国际膝关节文献委员会和膝关节损伤与骨关节炎结局评分疼痛域评分分别满足20分和12分改善的双重标准阈值,建立了治疗与对照组应答者数量有统计学显著差异的主要结局测量指标。1年方案的优势评估指标差一点错过,导致该试验于2019年终止。最终,这种疗法没有被FDA批准使用。这一案例的历史:压制一种生物学上安全和有效的治疗方法,突显了在美国通过监管程序向患者提供科学合理产品的复杂过程中的障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Next Generation Cartilage Repair and the Pre-arthroplasty Patient

The NeoCart implant (Histogenics Corporation, Waltham, MA; Ocugen Inc., Malvern, PA) is a cell-based therapeutic for the restoration of articular cartilage defects. The implant is composed of a type I collagen scaffold, inoculated with expanded autologous chondrocytes, and preconditioned under hydrostatic loading and low oxygen tension. The process was designed to create an autogenous chondrogenic construct for application during a surgical biologic reconstruction procedure for patients with symptomatic cartilage disease. Favorable pre-clinical basic science and animal studies characterizing the regenerative potential of NeoCart led to application for United States Food and Drug Administration (FDA) approval as the first autologous tissue therapeutic for articular cartilage restoration, beginning with a Phase I safety trial in 2003.

Deemed safe in Phase I and efficacious in Phase II relative to “standard of care” microfracture, a Phase III randomized controlled superiority trial versus microfracture was authorized by FDA in 2010. The primary outcome measure of a statistically significant difference in the number of responders to treatment versus control based on meeting a dual-criteria threshold of >20-point and >12-point improvement in International Knee Documentation Committee and Knee Injury and Osteoarthritis Outcome Score pain domain scores, respectively, was established. The 1-year protocol assessment metric for superiority was narrowly missed, which led to termination of the trial in 2019. Ultimately, the therapy was not approved for use by the FDA. The history of this case example: quelching a biologically safe and effective therapeutic, highlights hurdles in the complex process of bringing scientifically sound products to patients through regulatory processes in the United States.

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来源期刊
CiteScore
0.60
自引率
0.00%
发文量
46
审稿时长
93 days
期刊介绍: Operative Techniques in Sports Medicine combines the authority of a textbook, the usefulness of a color atlas and the timeliness of a journal. Each issue focuses on a single clinical condition, offering several different management approaches. It''s the easiest way for practitioners to stay informed of the latest surgical advancements and developments.
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